Biochemistry Chapter 23: Metabolism and Energy Production

Chapter Twenty Three: Metabolism and Energy Production

• Homework assignments (no credit): 1-16, 25-32, 35-39, 45-48, 53-65, 67, 73, 75, 77, 79, 81, 83, 87, 91

The Citric Acid Cycle

• A series of reactions connecting acetyl CoA (from stage 2) to electron transport and ATP synthesis (in stage 3).

Stages of Catabolism

• Stage 1: Digestion and hydrolysis of complex molecules (proteins, polysaccharides, lipids, cell membrane) into smaller molecules (amino acids, glucose, fatty acids).
• Stage 2: Degradation and partial oxidation of smaller molecules. This includes glycolysis for glucose.
• Stage 3: Further oxidation of molecules to CO2, H2O, and energy for ATP synthesis. This involves the citric acid cycle and electron transport chain.

The Citric Acid Cycle (Stage 3)

• Operates under aerobic conditions.
• Oxidizes acetyl CoA to CO2.
• Also known as the tricarboxylic acid (TCA) cycle or Krebs cycle.
• Named after citric acid, formed in the first reaction.

Citric Acid Cycle Overview

• Eight reactions oxidize acetyl CoA, producing CO2 and high-energy compounds (FADH2, NADH, GTP).
• Includes reactions like condensation, dehydration, hydration, oxidation, reduction, and hydrolysis.

Reaction 1: Formation of Citrate

• Citrate synthase catalyzes the condensation of acetyl CoA (2C) with oxaloacetate (4C) to form citrate (6C).
• The energy for this condensation comes from the hydrolysis of the high-energy thioester bond in acetyl CoA.

Reaction 2: Isomerization

• Citrate is rearranged to isocitrate (a secondary alcohol).
• Aconitase catalyzes this isomerization. Citrate initially has a tertiary alcohol group, which is converted to a secondary alcohol.

Reaction 3: Oxidation, Decarboxylation

• Isocitrate undergoes oxidation and decarboxylation, converting a carboxylate group to CO2, by isocitrate dehydrogenase.
• Hydrogen ions and electrons are removed from isocitrate, reducing NAD+ to NADH and H+.

Reaction 4: Oxidation, Decarboxylation

• a-Ketoglutarate (5C), undergoes decarboxylation to form succinyl CoA (4C), catalyzed by a-ketoglutarate dehydrogenase.
• The oxidation of the thiol group in HS–CoA provides electrons and hydrogen ions used to reduce NAD⁺ to NADH and H⁺.

Reaction 5: Hydrolysis

• A high-energy thioester bond in succinyl CoA is hydrolyzed by succinyl CoA synthetase.
• This process transfers energy to produce GTP (a high-energy compound similar to ATP) from GDP and phosphate.

Reaction 6: Oxidation

• Succinate is oxidized to fumarate and a C=C bond, catalyzed by succinate dehydrogenase.
• Two H atoms are lost from succinate which reduce FAD to FADH2.

Reaction 7: Hydration

• Water is added to the double bond of fumarate by fumarase to form malate, a secondary alcohol.

Reaction 8: Oxidation

• Malate, catalyzed by malate dehydrogenase, is oxidized to oxaloacetate (a carbonyl group)
• The oxidation releases hydrogen ions and electrons, reducing NAD+ to NADH and H+. This produces another molecule of NADH + H+

Summary, Citric Acid Cycle

• Detailed summary including products of one turn of the citric acid cycle (2 CO2, 3 NADH + 3H+, 1 FADH2, 1 GTP (1 ATP), 1 HS-CoA)

Electron Transport

• Reduced coenzymes (NADH and FADH2) from glycolysis, pyruvate oxidation, and the citric acid cycle are oxidized to provide energy for ATP synthesis.
• In the respiratory chain, hydrogen ions and electrons pass from one carrier to another until they combine with oxygen to form H2O. This creates an electrochemical gradient.
• The released energy drives the synthesis of ATP through oxidative phosphorylation.

Electron Transport System

• Contains five protein complexes (I, II, III, IV, V), two electron carriers (coenzyme Q and cytochrome c).
• These components are located in the inner mitochondrial membrane.
• They carry electrons between protein complexes and the inner mitochondrial membrane.

Glycolysis, Citric Acid Cycle Results

• Table summarizing ATP and reduced coenzyme (NADH and FADH2) yields from glucose oxidation via glycolysis, pyruvate oxidation and the citric acid cycle. (2 ATP, 2 NADH from glycolysis ,2 NADH from pyruvate oxidation, 2 FADH2 and 6 NADH from citric acid cycle)

Electron Transport Chain

• A series of protein complexes within the mitochondrial membrane that transfers electrons from NADH and FADH2 to oxygen, producing a proton gradient.
• This gradient drives ATP synthesis.

NADH to Complex I

• Electron transport starts when hydrogen ions and electrons are transferred from NADH to Complex I.
• The loss of hydrogen from NADH regenerates NAD+ enabling more oxidation in pathways like the citric acid cycle.
• Hydrogen ions and electrons are transferred to the CoQ which forms CoQH2.

Complex I, Electron Transfer

• Pumps four H+ ions into the intermembrane space for every two electrons passing from NADH to CoQ.
• This creates a hydrogen ion gradient, generating energy.

Coenzyme Q

• Also known as ubiquinone, it accepts one or two electrons.
• Lipid-soluble, readily diffuses into the membrane.
• Carries electrons from Complexes I and II to Complex III.

Complex II

• The enzyme succinate dehydrogenase from the citric acid cycle.
• CoQ obtains electrons directly from FADH2.
• Produces FAD which becomes available to oxidize more substrates.
• No H+ ions pumped into the intermembrane space.

CoQH2 to Complex III

• CoQH2 obtained from Complexes I and II transfers electrons to Complex III.
• Two electrons from CoQH2 are transferred to a series of iron-containing proteins (cytochromes) found in complex III.
• Complex III generates energy by pumping H+ ions from the matrix to the intermembrane space.

Cytochrome c

• A water-soluble protein containing Fe3+/Fe2+ that can only transfer one electron at a time.
• Moves electrons from Complex III to Complex IV.
• For each CoQH2 molecule, two cytochrome c molecules are required.

Complex IV

• Four electrons from four cytochrome c molecules move to electron carriers in Complex IV.
• Hydrogen ions and oxygen combine to form two molecules of water.
• The released energy pumps H+ ions from the mitochondrial matrix to the intermembrane space to create a proton gradient.

Oxidative Phosphorylation

• Energy from electron transport is coupled to the production of ATP.
• The chemiosmotic model links electron transport energy to ATP synthesis.
• Complexes I, III, and IV operate as proton pumps, generating a proton gradient in the intermembrane space.
• The energy from the flow of protons back into the matrix drives ATP synthesis by ATP synthase.

Oxidative Phosphorylation, ATP

• In the chemiosmotic model, protons return to the matrix through ATP synthase (Complex V), generating energy for ATP synthesis from ADP and phosphate.
• This process links electron transport energy to ATP synthesis.

Electron Transport and ATP Synthesis

• NADH oxidation at Complex I yields 2.5 ATPs.
• FADH2 oxidation at Complex II yields 1.5 ATPs.

Problem

• Classify the following as products of the citric acid cycle or the electron transport chain: CO2, FADH2, NAD+, NADH, and H2O.

ATP from Oxidation of Glucose

• Table presenting the ATP yield from the complete oxidation of one glucose molecule, including glycolysis, oxidation and decarboxylation, and the citric acid cycle.

Complete Oxidation of Glucose

• Summary diagram showing the process of glucose oxidation, including stages (glycolysis, pyruvate oxidation/malate shuttle, citric acid cycle, and electron transport chain) yielding a net 32 ATP.

Explore Chapter 23 focusing on metabolism and energy production, including the intricate processes of the Citric Acid Cycle. This quiz covers stages of catabolism, from digestion to ATP synthesis, providing a comprehensive understanding of biochemical energy transformation.